A Case of Diabetic Chorea Secondary to Appetite Loss Due to COVID-19 Vaccination.

A 76-year-old woman with type 2 diabetes mellitus was admitted to our hospital with a complaint of involuntary movements of the limbs and face. Brain MRI demonstrated a bilateral high signal of putamen on the T1 weighted image, and she was diagnosed with diabetic chorea. She took a second dose of the COVID-19 vaccine 28 days before admission and lost her appetite. Consequently, her HbA1c level on admission decreased from 13.5% to 10.0% in 28 days. This case suggests that diabetic chorea could be induced by the rapid amelioration of a hyperglycemic state due to appetite loss after COVID-19 mRNA vaccination.

Anemia combined with albuminuria increases the risk of cardiovascular and renal events, regardless of a reduced glomerular filtration rate, in patients with type 2 diabetes: a prospective observational study.

Aim: The incidence of cardiovascular and renal events was investigated in patients with type 2 diabetes who were classified according to anemia and the components of dialysis-independent chronic kidney disease (CKD) in a prospective observational study. Methods: A population of 778 Japanese patients with type 2 diabetes was prospectively analyzed for 4 years. The outcomes were the incidence of cardiovascular events and renal events. Results: In all subjects, the incidence of cardiovascular and renal events was found to be 5% and 11%, respectively. Even after adjusting for a reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m2), the incidence of cardiovascular events was significantly higher (hazard ratio [HR]: 5.73) in patients with anemia and albuminuria than in those without anemia and albuminuria. The incidence of renal events was significantly higher in patients with no anemia and albuminuria (HR: 2.93) and further in those with anemia and albuminuria (HR: 7.56) than in those without anemia and albuminuria even after adjusting for a reduced eGFR. Conclusion: Anemia combined with albuminuria is a risk factor for vascular events in patients with type 2 diabetes, regardless of the eGFR. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00637-x.

Exacerbations of Idiopathic Systemic Capillary Leak Syndrome following BNT162b2 mRNA COVID-19 Vaccine (Pfizer-BioNTech).

A Japanese man experienced three episodes of hypovolemic shock and was diagnosed with systemic capillary leak syndrome (SCLS). He developed SCLS exacerbation 2 days after receiving a second dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine, 1 year after the third episode. After fluid therapy and albumin administration, we initiated terbutaline and theophylline prophylaxis for SCLS. A literature review revealed that SCLS attacks often occur 1-2 days after the second COVID-19 vaccination. Patients with a history of SCLS should avoid COVID-19 vaccination and be carefully monitored for 1-2 days if they receive the vaccine.

Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study.

BACKGROUND: This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. METHODS: This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. RESULTS: During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p = .034) and death (HR 1.64; 95% CI 1.24-2.16; p = .001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups. CONCLUSIONS: In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

Constipation Is a Frequent Problem Associated with Vascular Complications in Patients with Type 2 Diabetes: A Cross-sectional Study.

Objective Diabetes is recognized as an underlying disease of constipation. However, the prevalence of constipation varies according to the diagnostic criteria applied. We investigated the prevalence of constipation based on the new guideline for constipation in Japanese patients with type 2 diabetes and examined the relationship with the clinical background, including diabetic vascular complications. Methods Questionnaire surveys including items concerning the diagnosis and treatment status of constipation were administered to 410 patients with type 2 diabetes. Results Although 29% of the patients considered that they had experienced constipation (self-judged), only 14% had consulted a physician about constipation. The prevalence of chronic constipation based on the guideline was 26%. After including laxative users, constipation was finally found in 36%. Despite the use of laxatives (n=81), 51% of the patients were still diagnosed with chronic constipation. Patients with constipation (chronic constipation or laxative use) were significantly older and had a longer duration of diabetes than those without constipation. The body mass index (BMI) of patients with constipation (24.9±3.8 kg/m2) was significantly lower than that of those without constipation (26.3±4.6 kg/m2). Diabetic neuropathy (49% vs. 32%) and coronary heart disease (CHD) (27% vs. 13%) were significantly more frequent in the patients with constipation than in those without constipation. A multivariate logistic regression analysis revealed that gender, BMI, diabetic neuropathy, insulin use, and CHD were significantly associated with constipation. Conclusion An accurate diagnosis of constipation is desirable in patients with type 2 diabetes because constipation is independently associated with CHD.

Efficacy of dulaglutide after switching from incretin-related drugs in patients with type 2 diabetes and inadequate glycemic control.

AIMS: The efficacy of dulaglutide was assessed according to the pretreatments administered before the initiation of dulaglutide in patients with type 2 diabetes. METHODS: In total, 89 patients treated using dulaglutide (0.75 mg, once a weekly) were investigated. The subjects were divided into the three groups based on the form in which therapy was started: additional therapy (n = 35), switched from dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 32) and switched from daily glucagon-like peptide-1 receptor agonists (GLP-1 RAs, n = 30). The changes in medication adherence were determined in the daily GLP-1 RAs group using questionnaire surveys. RESULTS: The HbA1c values significantly decreased after the initiation of dulaglutide in all groups (additional therapy group, - 1.4 ± 1.6%; DPP-4 inhibitors group, - 1.2 ± 1.3%; and daily GLP-1 RAs group, - 0.5 ± 0.7%). Forty-six percent of the subjects in the daily GLP-1 RAs group reported that the incidence of forgetting injections of GLP-1 RA was decreased. The reduction of HbA1c was significantly greater in the subjects who reported a decrease in the incidence of forgetting injections (0.9 ± 0.9%) in comparison to those in which there was no change (0.1 ± 0.4%). CONCLUSIONS: Dulaglutide is considered effective in patients with type 2 diabetes and inadequate glycemic control, regardless of whether their pretreatment includes daily GLP-1 RA treatment.

Comparison of the effects of frequent versus conventional nutritional interventions in patients with type 2 diabetes mellitus: A randomized, controlled trial.

AIMS/INTRODUCTION: This randomized controlled trial aimed to determine whether frequent nutritional education improves the clinical parameters associated with the onset and progression of diabetic kidney disease in type 2 diabetes mellitus patients. MATERIALS AND METHODS: A total of 96 patients with type 2 diabetes and diabetic kidney disease were randomly assigned to the intensive intervention group that received nutritional education at every outpatient visit, and the usual intervention group that received nutritional education once a year. The anthropometric parameters, blood pressure, blood chemistry, albuminuria, protein and salt intake, and prescribed medications of 87 patients who completed the 2-year follow up were analyzed. RESULTS: In the intensive intervention group, body mass index and salt intake significantly decreased over the study period. Hemoglobin A1c levels and body fat percentage were significantly lower in the intensive intervention group than in the usual intervention group. At the end of the 2-year intervention period, the intensive intervention group had significantly lower salt intake (8.1 vs 9.4 g/day) than the usual intervention group. A significant positive correlation was found between salt intake and albuminuria in the overall group and intensive intervention group (r = 0.26, P = 0.02, and r = 0.36, P = 0.02, respectively). The intensive intervention group had a significantly lower insulin use rate than the usual intervention group after the 2-year intervention period (18% vs 42%). No differences were found in estimated glomerular filtration rate and albuminuria. CONCLUSION: Intensive nutritional education is useful for alleviating the risk factors associated with the onset and progression of diabetic kidney disease.

Combined changes in albuminuria and kidney function and subsequent risk for kidney failure in type 2 diabetes.

INTRODUCTION: Changes in albuminuria or estimated glomerular filtration rate (eGFR) can be used as a surrogate endpoint of end-stage kidney disease (ESKD) in people with type 2 diabetes. We investigated whether the combined changes in albuminuria and eGFR are more strongly associated with future risk of ESKD. RESEARCH DESIGN AND METHODS: Using data from a multicenter observational cohort study of people with type 2 diabetes, we evaluated the association of percentage change in urine albumin to creatinine ratio (UACR) and/or annual change in eGFR over 2 years with subsequent ESKD risk. RESULTS: Among 1417 patients with repeated albuminuria and eGFR over 2 years, 129 (9.1%) developed ESKD. Patients with >30% UACR decline had lower ESKD risk (HR 0.47; 95% CI 0.29 to 0.77), whereas those with >30% UACR increase had higher ESKD risk (HR 2.31; 95% CI 1.52 to 3.51), compared with those with minor UACR change. Patients with greater eGFR decline had an increased ESKD risk than those with minor eGFR change (a decline of <2.5 mL/min/1.73 m2/year): HR 4.19 (95% CI 1.87 to 9.38) and 2.89 (95% CI 1.32 to 6.33) for those with a decline of >5 and 2.5-5 mL/min/1.73 m2/year, respectively. When the combined changes in UACR and eGFR were used, the highest ESKD risk (HR 5.60; 95% CI 2.08 to 15.09) was observed among patients with >30% UACR increase and an eGFR decline of >5 mL/min/1.73 m2/year compared with those with a minor change in UACR and eGFR. CONCLUSIONS: Combined changes in albuminuria and eGFR over 2 years were strongly associated with future risk of kidney failure in patients with type 2 diabetes.

Different renoprotective effects of luseogliflozin depend on the renal function at the baseline in patients with type 2 diabetes: A retrospective study during 12 months before and after initiation.

AIMS: The safety and efficacy, particularly, the factors associated with the renal prognosis, were assessed over 12 months after the initiation of luseogliflozin therapy in Japanese patients with type 2 diabetes and renal impairment. METHODS: In total, 238 patients treated with luseogliflozin (2.5 mg, once daily) were studied as the safety analysis set. Two hundred and two subjects whose medication was continued over 12 months were investigated as the full analysis set. The subjects were divided into 3 groups based on the estimated glomerular filtration rate (eGFR): high eGFR (n = 49), normal eGFR (n = 116) and low eGFR (n = 37) groups. RESULTS: The body weight, systolic blood pressure, HbA1c and urinary protein excretion gradually decreased from baseline in all eGFR groups. While the eGFR was significantly reduced from baseline in the high and normal eGFR groups, the eGFR did not significantly differ over time in the low eGFR group. There was no marked difference in the frequency of adverse events that were specific for SGLT2 inhibitors among the 3 groups in the safety analysis set. CONCLUSIONS: Luseogliflozin can preserve the renal function in the medium term in patients with type 2 diabetes and renal impairment without an increase in specific adverse events.

The prognosis of subjects showing a reduced estimated glomerular filtration rate without albuminuria in Japanese patients with type 2 diabetes: a cohort study for diabetic kidney disease.

BACKGROUND: To determine the renal and cardiovascular prognosis and all-cause mortality of Japanese patients with type 2 diabetes showing a reduced estimated glomerular filtration rate (eGFR) without albuminuria. METHODS: A population of 675 patients with type 2 diabetes was prospectively observed for 4 years to determine the renal and cardiovascular outcomes and mortality. The subjects were divided into the four groups: those with a preserved eGFR and no albuminuria (n = 306), a preserved eGFR and albuminuria (n = 151), a reduced eGFR and no albuminuria (n = 96), and a reduced eGFR and albuminuria (n = 122). The Cox proportional hazard model and Fine and Gray method were used to assess between-group differences in the risk of mortality and cardiovascular events. RESULTS: In the group with a reduced eGFR, the eGFR value did not significantly change in the subjects without albuminuria (0 ± 8 mL/min/1.73 m2), whereas it decreased continuously in those with albuminuria (-6 ± 12 mL/min/1.73 m2). The incidence of cardiovascular events was significantly (P = 0.03) higher in the subjects with albuminuria (17%) than those without albuminuria (7%) in the group with a reduced eGFR. Cardiovascular events were significantly (P < 0.01) more frequent in the group with a reduced eGFR than in those with a preserved eGFR in both subjects with and without albuminuria. CONCLUSIONS: The risk of end-stage kidney disease in non-albuminuric subjects with a reduced eGFR is considered to be low. We should focus on cardiovascular prognosis, because these patients are still at high risk of cardiovascular events, even though the prognosis is better in comparison to albuminuric patients.

Hypermetabolism of glutathione, glutamate and ornithine via redox imbalance in methylglyoxal-induced peritoneal injury rats.

Peritoneal dialysis (PD) is a blood purification treatment for patients with reduced renal function. However, the peritoneum is exposed to oxidative stress during PD and long-term PD results in peritoneal damage, leading to the termination of PD. Methylglyoxal (MGO) contained in commercial PD fluids is a source of strong oxidative stress. The aim of this study was to clarify the mechanism of MGO-induced peritoneal injury using metabolome analysis in rats. We prepared peritoneal fibrosis rats by intraperitoneal administration of PD fluids containing MGO for 21 days. As a result, MGO-induced excessive proliferation of mesenchymal cells with an accumulation of advanced glycation end-products (AGEs) at the surface of the thickened peritoneum in rats. The effluent levels of methionine sulfoxide, an oxidative stress marker and glutathione peroxidase activity were increased in the MGO-treated rats. The levels of glutathione, glutamate, aspartate, ornithine and AGEs were also increased in these rats. MGO upregulated the gene expression of transporters and enzymes related to the metabolism of glutathione, glutamate and ornithine in the peritoneum. These results suggest that MGO may induce peritoneal injury with mesenchymal cell proliferation via increased redox metabolism, directly or through the formation of AGEs during PD.

Comparison of the changes in the factors associated with the renal prognosis of non-elderly and elderly subjects treated with empagliflozin- a retrospective observation study in Japanese patients with type 2 diabetes.

PURPOSE: The factors associated with the renal prognosis over six months after the initiation of empagliflozin were compared between the non-elderly and elderly Japanese patients with type 2 diabetes. PATIENTS AND METHODS: In total, 132 patients treated with empagliflozin (10 mg, once daily) were studied as the safety analysis set. One hundred ten subjects whose medications were not changed during the observation period were investigated as the full analysis set to assess the effectiveness. The subjects were divided into two groups: non-elderly subjects (n=72) of<65 years of age and elderly subjects (n=38) of≥65 years of age. RESULTS: Although the body weight and HbA1c, AST, ALT and γ-GTP levels were significantly reduced in both the non-elderly and elderly subjects, blood pressure, eGFR and urinary protein excretion were only significantly decreased in the non-elderly subjects. The hemoglobin, hematocrit and serum HDL-cholesterol levels were significantly elevated in both groups. The change in eGFR showed a significant positive association with the change in blood pressure. The change in urinary protein excretion tended to be correlated with the change in blood pressure. CONCLUSION: Although renoprotective effects might be limited, empagliflozin can safely and effectively improve metabolic parameters, even in elderly subjects.

Changes in medication adherence and unused drugs after switching from daily dipeptidyl peptidase-4 inhibitors to once-weekly trelagliptin in patients with type 2 diabetes.

AIMS: The changes in patients' satisfaction with the treatment, medication adherence and unused drugs before and after switching from daily DPP-4 inhibitors to once-weekly trelagliptin administration were prospectively investigated in patients with type 2 diabetes. METHODS: After excluding 46 patients who declined to switch from daily DPP-4 inhibitors, 79 subjects were included in the present study. The clinical parameters and results of questionnaire surveys regarding satisfaction with treatment as well as impressions of the amount of medicine/number of doses, medication adherence, and unused drug were examined at the baseline and 3 months after switching from daily DPP-4 inhibitors to trelagliptin in 75 patients with type 2 diabetes. RESULTS: Although the value of HbA1c did not change (7.0% ±â€¯0.5% to 7.0% ±â€¯0.6%), the scores representing satisfaction with the treatment (25.2 ±â€¯6.4 to 26.4 ±â€¯6.0), impression of the amount of medicine (-0.3 ±â€¯1.0 to 0.3 ±â€¯1.0) and number of doses (0.3 ±â€¯1.0 to 0.8 ±â€¯0.6), and medication adherence (0.8 ±â€¯0.4 to 0.9 ±â€¯0.3) as assessed by the questionnaire surveys were significantly improved after switching from DPP-4 inhibitors. The self-reported amount of unused drugs was significantly reduced after switching. CONCLUSIONS: Switching from daily DPP-4 inhibitors to once-weekly trelagliptin improved the satisfaction with the treatment, impression of the prescribed medicine and medication adherence in the type 2 diabetic patients who expresses a desire to reduce their prescription medicines. In such patients, improvements in the glycemic control and long-term prognosis might be expected through the reduction of unused drugs.

Multiple Sclerosis Drug Fingolimod Induces Thrombotic Microangiopathy in Deoxycorticosterone Acetate/Salt Hypertension.

We examined whether fingolimod (FTY720), an S1PR (sphingosine-1-phosphate receptor) modulator, has beneficial or harmful effects on mineralocorticoid/salt-induced renal injury. Uninephrectomized rats on 0.9% NaCl/0.3% KCl drinking solution were randomly divided into control, control+FTY720, deoxycorticosterone acetate (DOCA), and DOCA+FTY720 groups and administered vehicle, vehicle+FTY720, DOCA+vehicle, and DOCA+FTY720 for 4 weeks, respectively. Only the DOCA+FTY720 group had reduced survival rates and showed hemolysis because of intravascular mechanical fragmentation of erythrocytes and thrombocytopenia. Both the DOCA+FTY720 and DOCA groups developed malignant hypertension, which was more severe in the DOCA+FTY720 group. In the DOCA+FTY720 group only, thrombotic microangiopathy involving severe renal arteriole endothelial cell injury was observed and was characterized by fibrinoid necrosis and onion-skin lesions in arterioles. There were fewer circulating endothelial progenitor cells in the DOCA+FTY720 group but more in the DOCA group compared with the control group. Expression levels of VEGF (vascular endothelial growth factor), S1PR1, and S1PR3 in renal arteriole endothelial cells were significantly greater in the DOCA+FTY720 and DOCA groups compared with the control group, with levels being similar between the 2 groups. Expression levels of endothelial nitric oxide synthase in renal arteriole endothelial cells were significantly lower in the DOCA+FTY720 group only. The control+FTY720 group showed reduced circulating endothelial progenitor cells but no significant functional or pathological changes in kidneys or changes in blood pressure. Exposure of uninephrectomized rats to DOCA/salt+FTY720 for 4 weeks induced renal arteriolar endothelial cell injury, resulting in the development of thrombotic microangiopathy. Consideration of this possibility is recommended when prescribing FTY720.

Estimated glomerular filtration rate decline and risk of end-stage renal disease in type 2 diabetes.

BACKGROUND: According to studies by the National Kidney Foundation and Food and Drug Administration, 30% and 40% declines in estimated glomerular filtration rate (eGFR) could be used as surrogate endpoints of end-stage renal disease (ESRD). However, the benefits of using these endpoints in diabetic patients remain unclear. METHODS: This cohort study comprised Japanese patients with type 2 diabetes; those with repeated serum creatinine measurements during a baseline period of 2 years (n = 1868) or 3 years (n = 2001) were enrolled. Subsequent risks of ESRD following eGFR declines were assessed. RESULTS: In the 2-year baseline analysis, the cumulative prevalence of -20%, -30%, -40%, and -53% changes in eGFR were 23.9%, 11.1%, 6.8%, and 3.7%, respectively. There were 133 cases (7.1%) of subsequent ESRD during a median follow-up period of 6.5 years. In the 3-year baseline analysis, the corresponding proportions were 28.1%, 14.0%, 7.7%, and 3.9%, respectively, with 110 participants (5.5%) reaching ESRD during a median follow-up period of 5.5 years. The adjusted hazard ratios of subsequent ESRD following -53%, -40%, -30%, and -20% changes in eGFR during the 2-year baseline period were 22.9 (11.1-47.3), 12.8 (6.9-23.7), 8.2 (4.3-15.5), and 3.9 (2.2-7.0), respectively when compared with the no changes in eGFR. In the 3-year baseline analysis, the corresponding risks were 29.7 (10.8-81.9), 18.4 (7.6-44.7), 12.8 (5.2-32.2), and 5.4 (2.3-12.8), respectively. In the subgroup analysis, similar trends were observed in patients with macroalbuminuria at baseline. CONCLUSIONS: Declines in eGFR were strongly associated with subsequent risk of ESRD in Japanese type 2 diabetic patients. In addition to 30% and 40% declines, a 20% decline in eGFR over 2 years could be considered as a candidate surrogate endpoint of ESRD in diabetic kidney disease.

Acquired von Willebrand Syndrome Complicating Nephrotic Syndrome: A Case of a Patient With Membranous Nephropathy.

Acquired von Willebrand syndrome (AVWS) is a rare clinical entity presenting with heterogeneous hemorrhagic manifestations, although some subsets of patients with AVWS may be asymptomatic until they are exposed to major trauma, an invasive procedure, or surgery. We herein report one such case in a 73-year-old male patient with nephrotic syndrome with a prolonged active partial thromboplastin time. We initially did not deal with this distinct abnormal clotting profile seriously, but persistent bleeding after a retroperitoneoscopic-assisted renal biopsy that allowed us to ascribe his nephrotic syndrome to membranous nephropathy fortuitously led to the discovery of concurrent AVWS. We feel that an accurate and prompt diagnosis as well as awareness of the disease remain a challenge for physicians and therefore strongly recommend the further accumulation of experiences similar to our own in a prospective manner. This report underscores the pitfalls associated with determining the bleeding risk, including an insufficient assessment and improper weighting of an abnormal clotting profile prior to the invasive procedure. Several management concerns that emerged in the current case are also discussed.

Pleuroperitoneal Communication and Ovarian Cancer Complicating Peritoneal Dialysis: A Case Report of a Patient with End-Stage Kidney Disease.

Peritoneal dialysis has been a widely accepted modality for treating end-stage kidney disease, but a regular dialysis schedule can be seriously disrupted by various comorbid conditions requiring surgical intervention. A 40-year-old woman who had been receiving peritoneal dialysis was sequentially but separately complicated by pleuroperitoneal communication and ovarian cancer. Despite the need for temporary interruption of her peritoneal dialysis schedule, it was successfully resumed after the relevant surgeries for each disease. Several concerns regarding overall postoperative dialytic management strategies, including how to deal with the peritoneal dialysis catheter during the postoperative period as well as how long peritoneal dialysis should be interrupted, which remain an unresolved issue in the field of nephrology, are also discussed.

Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease.

Fibroblast growth factor 21 (FGF21) is an endocrine factor that regulates glucose and lipid metabolism. Circulating FGF21 predicts cardiovascular events and mortality in type 2 diabetes mellitus, including early-stage chronic kidney disease, but its impact on clinical outcomes in end-stage renal disease (ESRD) patients remains unclear. This study enrolled 90 ESRD patients receiving chronic hemodialysis who were categorized into low- and high-FGF21 groups by the median value. We investigated the association between circulating FGF21 levels and the cardiovascular event and mortality during a median follow-up period of 64 months. A Kaplan-Meier analysis showed that the mortality rate was significantly higher in the high-FGF21 group than in the low-FGF21 group (28.3% vs. 9.1%, log-rank, P = 0.034), while the rate of cardiovascular events did not significantly differ between the two groups (30.4% vs. 22.7%, log-rank, P = 0.312). In multivariable Cox models adjusted a high FGF21 level was an independent predictor of all-cause mortality (hazard ratio: 3.98; 95% confidence interval: 1.39-14.27, P = 0.009). Higher circulating FGF21 levels were associated with a high mortality rate, but not cardiovascular events in patient with ESRD, suggesting that circulating FGF21 levels serve as a predictive marker for mortality in these subjects.

Therapeutic Dilemmas Regarding Anticoagulation: An Experience in a Patient with Nephrotic Syndrome, Pulmonary Embolism, and Traumatic Brain Injury.

Patients with active bleeding complications who concomitantly develop overt pulmonary embolism (PE) present distinct therapeutic dilemmas, since they are perceived to be at substantial risk for the progression of the embolism in the absence of treatment and for aggravation of the hemorrhagic lesions if treated with anticoagulants. A 76-year-old patient with nephrotic syndrome, which is associated with an increased risk of thromboembolism, concurrently developed acute PE and intracranial bleeding because of traumatic brain injury. In this case, we prioritized the treatment for PE with the intravenous unfractionated heparin followed by warfarinization. Despite the transient hemorrhagic progression of the brain contusion after the institution of anticoagulation, our patient recovered favorably from the disease without any signs of neurological compromise. Several conundrums regarding anticoagulation that emerged in this case are also discussed.

Minimal Change Nephrotic Syndrome Sequentially Complicated by Acute Kidney Injury and Painful Skin Ulcers due to Calciphylaxis.

Calciphylaxis is rare cutaneous manifestation associated with painful skin ulceration and necrosis. It primarily occurs in patients with end-stage chronic kidney disease. In this report, we would like to show our experience with a male patient presenting with minimal change nephrotic syndrome that was sequentially complicated by acute kidney injury and painful ulcerative cutaneous lesions due to calciphylaxis. There seemed to be several contributing factors, including a disturbance of the patient's mineral metabolism and the systemic use of glucocorticoids and warfarin. Various concerns regarding the diagnostic and therapeutic conundrums that were encountered in the present case are also discussed.